Patent GB-1158570-A (GB)
Title: Diacylthiamines and processes for preparation thereof
IPC: C07D415/00
Filed: 1966-11-14
Abstract: 1,158,570. Diacylthiamines. DAINIPPON PHARMACEUTICAL CO. Ltd. 14 Nov., 1966 [18 Nov., 1965; 19 Nov., 1965; 2 Dec., 1965; 18 Dec., 1965; 20 Dec., 1965; 4 June, 1966; 18 June, 1966; 24 June, 1966 (2)], No. 50933/66. Heading C2V. The invention comprises diacylthiamines of formula where one of R and R<SP>1</SP> is nicotinoyl and the other is nicotinoyl, benzoyl (which may be alkyl- and/ or alkoxy-substituted), alkanoyl (which may be alkoxy-, halogen- and/or phenyl-substituted) or furoyl, and N-oxides and pharmaceutically acceptable acid addition salts thereof. The compounds are prepared by reacting an in organic acid salt of O-acylthiamine of formula (where X is the anion of the inorganic acid) or S-acylthiamine of formula with an acylating agent Y-R where R and R<SP>1</SP> are as above and Y is the residue of the acylating agent; the compounds also may be prepared by acylating an inorganic acid salt of thiamine with an acylating agent Y<SP>1</SP>-R<SP>1</SP> in the presence of a strong base, and then acylating with an acylating agent Y-R in the presence of a strong base, R and R<SP>1</SP> being as above and Y and Y<SP>1</SP> being residues of the acylating agents. In examples thiamine chloride hydrochloride is reacted with nicotinic anhydride to obtain O,S-dinicotinylthiamine, and with nicotinylethylcarbonate to obtain O,S- dinicotinylthiamine; S-nicotinylthiamine is reacted with nicotinyl chloride hydrochloride to obtain O,S-dinicotinylthiamine; O-nicotinylthiamine chloride hydrochloride is reacted with nicotinic anhydride to obtain O,S-dinicotinylthiamine; S-benzoylthiamine is reacted with nicotinic anhydride, with nicotinyl chloride hydrochloride and with nicotinyl chloride to obtain S-benzoyl-O-nicotinylthiamine; O-nicotinylthiamine chloride hydrochloride is reacted with benzoyl chloride to obtain S-benzoyl-O nicotinylthiamine; S-nicotinylthiamine is reacted with sodium hydroxide and then with benzoyl chloride to obtain S-benzoyl-O-nicotinylthiamine; S-nicotinylthiamine is reacted with benzoyl chloride and with benzoic acid to obtain O-benzoyl-S-nicotinylthiamine; O-benzoylthiamine chloride hydrochloride is reacted with nicotinic anhydride to obtain O-benzoyl-S- nicotinylthiamine; S-benzoylthiamine is reacted with sodium hydroxide and then with nicotinic anhydride to obtain O-benzoyl-S- nicotinylthiamine; O-benzoylthiamine chloride hydrochloride is reacted with nicotinyl ethyl carbonate to obtain O-benzoyl-S-nicotinylthiamine; O-nicotinylthiamine chloride hydrochloride is reacted with butyric anhydride to obtain S-butyroyl-O-nicotinylthiamine, and with acetic anhydride, propionic anhydride, isobutyric anhydride and n -valeryl chloride to obtain the corresponding S-acetyl-, S-propionyl-, S-isobutyroyl- and S-valeryl-compounds; S- nicotinylthiamine is reacted with sodium hydroxide and then with propionic anhydride to obtain O-nicotinyl-S-propionylthiamine; O- nicotinylthiamine chloride hydrochloride is reacted with palmitoyl chloride to obtain O- nicotinyl-S-palmitoylthiamine and with stearoylchloride to obtain O-nicotinyl-S-stearoylthiamine; nicotinyl chloride hydrochloride is reacted with S-valeryl-, S-butyroyl-, S-isobutyroyl- and S-acetylthiamine to obtain the corresponding O-nicotinyl compounds; nicotinic anhydride is reacted with S-isobutyroylthiamine to obtain S-isobutyroyl-O-nicotinylthiamine; nicotinic anhydride is reacted with O-acetyl-, O-propionyl-, O-valeryl- and O- butyroyl thiamine chloride hydrochloride to obtain the corresponding S-nicotinyl compounds; O-butyroylthiamine chloride hydrochloride is reacted with nicotinylchloride hydrochloride to obtain O-butyroyl-S-nicoinylthiamine; S-butyroylthiamine is reacted with sodium hydroxide and then with nicotinic anhydride to obtain O-butyroyl-S-nictotinylthiamine; O-lauroylthiamine chloride hydrochloride is reacted with nicotinylethyl carbonate to obtain O-lauroyl-S-nicotinylthiamine; S- nicotinylthiamine is reacted with acetic anhydride, propionic anhydride, propionyl chloride and butyric anhydride to obtain the corresponding O-acetyl-, O-propionyl- and O-butyroyl-compounds; S-p-methyl benzoyl-, S-p-methoxybenzoyl-, S-benzoyl- and S-isobutyroyl thiamine are reacted with nicotinyl chloride hydrochloride to obtain the corresponding O-nicotinyl compounds; thiamine chloride hydrochloride is reacted with S-nicotinyl-N,N-dimethyldithiocarbamate and then with methoxyacetic anhydride to obtain S-methoxyacetyl-O- nicotinylthiamine; S-furoylthiamine is reacted with nicotinyl chloride to obtain S-furoyl-O- nicotinylthiamine; thiamine chloride hydrochloride is reacted with S-nicotinyl-N,N-dimethyldithiocarbamate and then with chloroacetic anhydride to obtain S-chloroacetyl-O- nicotinylthiamine; O-nicotinylthiamine chloride hydrochloride is reacted with S-benzoyl-N, N-dimethyldithiocarbamate to obtain S-benzoyl-O-nicotinylthiamine; O-benzoylthiamine chloride hydrochloride is reacted with S-nicotinyl-N,N-dimethyldithiocarbamate to obtain O- benzoyl-S-nicotinylthiamine; O-nicotinylthiamine chloride is reacted with 2,4-dinitrophenylisobutyrate to obtain S-isobutyroyl-O-nicotinylthiamine; acid addition salts and N-oxides are obtained from some of the products.